Erlotinib Hydrochloride in Reducing Duodenal Polyp Burden in Patients With Familial Adenomatous Polyposis at Risk of Developing Colon Cancer

Overview

About this study

This phase II trial studies the side effects of erlotinib hydrochloride and how well it works in reducing duodenal polyp burden in patients with familial adenomatous polyposis at risk of developing colon cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Pre-Registration Inclusion Criteria:

  • Diagnosis of familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP), defined as at least one of the following:
    • Genetic diagnosis with confirmed APC mutation (clinical CLIA certified lab or research testing);
    • Obligate carrier;
    • Clinical diagnosis of classic FAP with ≥ 100 colorectal adenomas status post colectomy and a family history of FAP;
    • Clinical diagnosis of FAP, based on personal and family history.
      • Note: This criterion requires documented review and agreement from either the Study Chair or the CPN Lead Investigator.
  • Age ≥ 18 and ≤ 69 years of age.
    • Note: Because no dosing or adverse event (AE) data are currently available on the use of erlotinib in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Willing to discontinue taking NSAIDS for 30 days prior to initiation of and during intervention.
    • Exception: Use of ≤ 81 mg daily or ≤ 650 mg weekly aspirin is allowed.
  • Willing to discontinue smoking for the duration of study intervention.
  • Willing to provide mandatory biospecimens as specified in the protocol.

Pre-Registration Exclusion Criteria:

  • Any prior treatment with erlotinib or other agent whose primary mechanism of action is known to inhibit EGFR.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib.
  • Use of potent CYP3A4 inhibitors, including but not limited to ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice.
  • Use of potent CYP3A4 inducers, including but not limited to rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's Wort.
  • Use of any other investigational agents ≤ 12 weeks prior to pre-registration.
  • Uncontrolled intercurrent illness or recent surgical procedure that in the opinion of the investigative team would limit compliance with study requirements, including, but not limited to:
    • Ongoing or active infection;
    • Symptomatic congestive heart failure;
    • Myocardial infarction ≤ 6 months prior to intervention;
    • Severely impaired lung function;
    • Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with study intervention;
    • Diagnosed liver disease, such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis;
    • Unstable angina pectoris;
    • Cardiac arrhythmia;
    • Psychiatric illness/social situations.
  • History of invasive malignancy ≤ 3 years prior to pre-registration.
    • Exception: adequately treated carcinoma of the cervix, carcinoma in situ, or basal or squamous cell carcinomas of the skin.
  • Individuals on anticoagulation medications who cannot safely discontinue the medication for at least 48 hours prior to the study endoscopy, as determined by the study investigator and/or participant’s primary healthcare provider.
  • History of any upper GI surgery that does not permit access to or evaluation of a 10 cm segment of the duodenum that includes the duodenal bulb; i.e. Whipple Procedure or similar.

Registration Inclusion Criteria:

  • ECOG performance status ≤ 1
  • Adequate bone marrow and organ function:
    • Leukocytes (WBC) ≥ 3,000/uL (≥ 2,500/uL for African-American participants);
    • Platelet count ≥ 100 x 109/L;
    • Hemoglobin ≥ 11.5 g/dL;
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN);
    • Alkaline phosphatase ≤ 1.5 x institutional upper limit of normal (ULN);
    • AST/SGOT ≤ 2 x institutional upper limit of normal (ULN);
    • ALT/SGPT ≤ 2 x institutional upper limit of normal (ULN);
    • Creatinine ≤ institutional upper limit of normal (ULN);
    • Urinary testing results within institutional limits of normal or deemed clinically insignificant.
  • Spigelman 2-3.
  • Not pregnant or breast feeding.
    • Note: The effects of erlotinib (Tarceva ®) on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. Breastfeeding should be discontinued if the mother is treated with erlotinib.
  • Willing to use adequate contraception to avoid pregnancy or impregnation until 2 weeks after discontinuing study agent.

Registration Exclusion Criteria:

  • Histologically-confirmed high grade dysplasia (HGD), cancer, or polyp burden that is not quantifiable.
  • Regular (≥ 2 times per week) use of drugs that alter the pH of the GI tract, such as proton pump inhibitors (PPI) and antacids.
    • Exceptions: Individuals who use prescription PPIs and have approval from their primary health care provider to replace the PPI with an H2 receptor agonist; i.e., ranitidine, for the duration of the trial will be eligible.
  • Gastrointestinal bleeding.
    • Note that the presence of any symptoms (dyspnea, fatigue, angina, weakness, malaise, melena, hematochezia, hematemesis, anemia, abdominal pain) will require clinical assessment to rule out gastrointestinal bleeding.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Niloy Jewel Samadder, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Paul Limburg, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20311160

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